The role and application of current pharmacological management in patients with advanced heart failure.

In the last decades, several classifications and definitions have been proposed for advanced heart failure (ADVHF) patients, including clinical, functional, hemodynamic, imaging, and electrocardiographic features. Despite different inclusion criteria, ADVHF is characterized by some common items, such as drug intolerance, low arterial pressure, multiple organ dysfunction, chronic kidney disease, and diuretic use dependency. Additional features include fatigue, hypotension, hyponatremia, and unintentional weight loss associated with a specific laboratory profile reflecting systemic multiorgan dysfunction. Notably, studies evaluating guideline-directed medical therapy recently endorsed by guidelines in stable HF, including the 4 drug classes all together (i.e., betablocker, mineral corticoid antagonist, renin angiotensin inhibitors/neprilysin inhibitors, and sodium glucose transporter inhibitors), remain scarcely analyzed in ADVHF and New York Heart Association (NYHA) Class IV. Additionally, due to the common conditions associated with advanced stages, the balance between drug tolerance and potential benefits of the contemporary use of all agents is questioned. Therefore, less hard endpoints, such as exercise tolerance, quality of life (QoL) and self-competency, are not clearly demonstrated. Specific analyses evaluating outcome and rehospitalization of each drug provided conflicting results and are often limited to subjects with stable conditions and less advanced NYHA class. Current European Society of Cardiology/American Heart Association (ESC/AHA) Guidelines do not indicate the type of treatment, dosage, and administration modalities, and they do not suggest specific indications for ADVHF patients. Due to these concerns, there is an impelling need to understand what drugs may be used as the first line, what management leads to the better outcome, and what is the best treatment algorithm in this setting. In this paper, we summarize the most common pitfalls and limitations for the use of the traditional agents, and we propose a personalized approach aiming at preserve drug tolerance and maintaining adverse event protection and satisfactory QoL.

Noncardiac comorbidity clustering in heart failure: an overlooked aspect with potential therapeutic door.

Heart failure is associated with a range of comorbidities that have the potential to impair both quality of life and clinical outcome. Unfortunately, noncardiac diseases are underrepresented in large randomized clinical trials, and their management remains poorly understood. In clinical practice, the prevalence of comorbidities in heart failure is high. Although the prognostic impact of comorbidities is well known, their prevalence and impact in specific heart failure settings have been overlooked. Many studies have described specific single noncardiac conditions, but few have examined their overall burden and grading in patients with multiple comorbidities. The risk of comorbidities in patients with heart failure rises with more advanced disease, older age, and increased frailty-three conditions that are poorly represented in clinical trials. The pathogenic links between comorbidities and heart failure involve many pathways and include neurohormonal overdrive, inflammatory activation, oxidative stress, and endothelial dysfunction. Such interactions may worsen prognoses, but details of these relationships are still under investigation. We propose a shift from cardiac-focused care to a more systemic approach that considers all noncardiac diseases and related medications. Some new drugs class such as ARNI or SGLT2 inhibitors could change prognosis by acting directly or indirectly on metabolic disorders and related vascular consequences.

Direct oral anticoagulants across the heart failure spectrum: the precision medicine era.

Heart failure (HF) is characterized by a pro-thrombotic state, which might aggravate its morbidity and, consequently, mortality. Several and commonly observed comorbidities, such as coronary artery disease, atrial fibrillation (AF), renal dysfunction, and diabetes often complicate HF, increasing the thromboembolic risk. In the past decade, direct oral anticoagulants (DOACs) have been approved for the treatment and prevention of stroke and embolic events in patients with nonvalvular AF. Due to their lower bleeding risk, these drugs are frequently used instead of warfarin; however, some controversies exist on their use in HF patients with or without comorbidities. Indeed, the management of anticoagulation in HF patients with underlying conditions is poorly investigated since these patients are underrepresented or excluded from randomized controlled trials. The aim of this research is to review current evidence on the use of DOACs in HF patients, also discussing their specific use in different clinical scenarios. Graphical abstract.

Screening, detection, and management of heart failure in the SARS-CoV2 (COVID-19) pandemic.

Observational studies suggest that a heart failure (HF) diagnosis carries a poor prognosis in subjects with severe SARS-CoV2 (COVID-19) infection, but it is unknown whether this association reflects direct myocardial damage due to COVID-19 or the consequence of preexisting cardiac defects and related cardiovascular disease (CVD) risk burden. Although the close relation between CVD and COVID-19 outcomes is well established, contrasting data exists about the occurrence of HF complications during COVID-19 infection. Therefore, a specific algorithm focused on diagnostic differentiation in acute patients distinguishing between acute HF and acute respiratory distress syndrome related to COVID-19 is needed. Further, several concerns exist for the management of patients with an uncertain diagnosis and acute dyspnea, the exact relationship existing between COVID-19 and HF. Therefore, the treatment for subjects with both COVID-19 and HF and which criteria may be defined for domiciliary or hospital management, remain poorly defined. Herein, we describe practices to be adopted in order to address these concerns and avoid further virus spread among patients, l and their familiars involved in such patients' care.

Prognostic Significance of an Early Echocardiographic Evaluation of Right Ventricular Dimension and Function in Acute Heart Failure.

OBJECTIVE: Sparse and contradictory data are available on the prognostic role of an early echocardiographic examination in patients with acute decompensated heart failure (ADHF). We planned a prospective study to illustrate which early echocardiographic parameter would be better related to prognosis in such patients. METHODS: In a consecutive series of patients with ADHF with either reduced (n=209) or preserved (n=172) left ventricular ejection fraction (LVEF), a complete echocardiographic examination was performed within 12 hours of admission. The endpoint of the study was death or rehospitalization at 6 months from hospital discharge. RESULTS: After 6 months from discharge, 73 died and 96 were rehospitalized due to cardiovascular causes. In multivariable analysis, a right ventricular end-diastolic diameter (RVEDD) >40 mm (P = .02), a tricuspid annular plane systolic excursion (TAPSE) <19 mm (P= .004), and an inferior vena cava diameter >22 mm (P = .02) were associated with 6-month events. LVEF and LV diastolic function were not predictive of events. Pulmonary artery systolic pressure (PASP) >45 mmHg and TAPSE/PASP <0.425 were associated with prognosis in univariate but not in multivariable analysis. Conversely, the TAPSE/RVEDD ratio (dichotomized at its median value of 0.461) was an independent predictor of outcome in multivariable analysis (P< .001). CONCLUSIONS: In patients hospitalized for ADHF, early echocardiographic identification of right ventricular dilatation and dysfunction predicts a poor outcome better than LV systolic and/or diastolic dysfunction.

The role of the kidney in acute and chronic heart failure.

Renal dysfunction affects approximately 30 to 50% of heart failure (HF) patients. The unfavourable relationship between heart and kidney dysfunction contributes to worse outcomes through several mechanisms such as inflammation, oxidative stress, impaired hydrosaline homeostasis, and diuretic resistance. Renal dysfunction not only carries important prognostic value both in acute and in chronic HF, but also is a potential precipitating factor after the first diagnosis. Because renal dysfunction encompasses different etiologies, a better understanding of its definition, incidence, and pathophysiology provides additional information. Although old and novel available biomarkers for the detection of renal dysfunction have been recently proposed, there is no general consensus regarding the terminology and definition of renal dysfunction in HF. Due to some specific pathophysiological mechanisms, renal impairment seems to be different on an individual patient level and, recognizing it in acute and chronic settings, could be useful to optimize decongestive treatment. For these reasons, in this review, we aim to describe and evaluate different phenotypes of renal dysfunction in acute and chronic HF and the possible management in these settings. KEY MESSAGES: • Chronic kidney dysfunction and worsening renal function are highly prevalent in acute heart failure and chronic heart failure and associated with poor outcomes. • This association is modified by the context in which it occurs, i.e. worsening renal function in the context of adequate decongestion in acute heart failure, or worsening renal function after initiation of neurohormonal blockers in chronic heart failure. • Future research should be aimed at elucidating the mechanisms involved in these differenct contexts, as well as alternative treatment approaches in the case of true worsening renal function.

Urgent need for individual mobile phone and institutional reporting of at home, hospitalized, and intensive care unit cases of SARS-CoV-2 (COVID-19) infection.

Approximately 90 days of the SARS-CoV-2 (COVID-19) spreading originally from Wuhan, China, and across the globe has led to a widespread chain of events with imminent threats to the fragile relationship between community health and economic health. Despite near hourly reporting on this crisis, there has been no regular, updated, or accurate reporting of hospitalizations for COVID-19. It is known that many test-positive individuals may not develop symptoms or have a mild self-limited viral syndrome consisting of fever, malaise, dry cough, and constitutional symptoms. However some individuals develop a more fulminant syndrome including viral pneumonia, respiratory failure requiring oxygen, acute respiratory distress syndrome requiring mechanical ventilation, and in substantial fractions leading to death attributable to COVID-19. The pandemic is evolving in a clustered, non-inform fashion resulting in many hospitals with preparedness but few or no cases, and others that are completely overwhelmed. Thus, a considerable risk of spread when personal protection equipment becomes exhausted and a large fraction of mortality in those not offered mechanical ventilation are both attributable to a crisis due to maldistribution of resources. The pandemic is amenable to self-reporting through a mobile phone application that could obtain critical information on suspected cases and report on the results of self testing and actions taken. The only method to understand the clustering and the immediate hospital resource needs is mandatory, uniform, daily reporting of hospital censuses of COVID-19 cases admitted to hospital wards and intensive care units. Current reports of hospitalizations are delayed, uncertain, and wholly inadequate. This paper urges all the relevant stakeholders to take up self-reporting and reporting of hospitalizations of COVID-19 as an urgent task in combating this devastating pandemic.

Clinical impact of oral antidiabetic medications in heart failure patients.

Heart failure (HF) is a common complication in patients with type 2 diabetes and it is closely associated with high morbidity and mortality rate. The incidence of cardiovascular events in patients with diabetes is related to high levels of glycemia, expressed by increase of HbA1c levels. However, there is little evidence to indicate that glycemic control can reduce the incidence of HF events in this population. Recently, several new antidiabetic drugs have been proposed although the exact clinical impact on heart failure occurrence and deterioration is under debate. Most common oral antidiabetic medication such as SGLT2, GLP-1 receptor agonist, metformin, and DPP4 inhibitor revealed peculiar metabolic and biomolecular signal effects. Moreover, the negative effects of thiazolidinediones on HF prognosis, on cardiac function, and exercise tolerance is of great interest. Conversely, several studies on GLP-1RA have highlighted many positive effects on cardiac myocytes, reducing apoptosis through cAMP/PKA/CRCB-mediated pathways protecting against oxidative stress. DPP-4 inhibitors have a controversial effect: saxagliptin and alogliptin may increase the risk of HF as opposed to vildagliptin and sitagliptin. Metformin increases myocardial ATP levels due to activation of 5-AMPK and this could explain the positive link between the drug and events rate reduction in diabetic patients with HF. The more interesting class of new drugs is SGLT2 inhibitors, that seems to have a positive effect on cardiac function by 38% reduction of HF incidence and mortality with empagliflozin treatment. In this review, we would analyze the specific effects of each class so as to better elucidate the clinical impact of antidiabetic drug on HF for guiding the clinicians in the choice of a best individualized therapy.

Pulmonary hypertension: a correct diagnosis for a suitable therapy in scleroderma patients.

Systemic sclerosis (SSc) is a heterogeneous disorder characterised by dysfunction of the endothelium and dysregulation of fibroblasts, resulting in excessive production of collagen, and abnormalities of the immune system. Progressive fibrosis of the skin and internal organs is a pathologic hallmark of the disease, resulting in major organ damage and failure. Pulmonary hypertension (PH) is frequent in patients with SSc and, pulmonary arterial hypertension (PAH) represents one of the main causes of death. PH is not a specific disease, but a haemodynamic condition characterized by a mean pulmonary pressure ≥25mmHg. In SSc, because of the great variability in clinical manifestation, it is possible to identify pulmonary hypertension due to left heart disease, PH due to respiratory disease or pulmonary arterial hypertension. The knowledge of PH and the right diagnosis are crucial to assess the most appropriate therapeutic strategy. In this article, the new classification criteria of PH have been examined taking into account the SSc clinical evolution and focusing on the different underlying pathogenetic mechanisms.

Loop diuretics in acute heart failure: beyond the decongestive relief for the kidney.

Current goals in the acute treatment of heart failure are focused on pulmonary and systemic decongestion with loop diuretics as the cornerstone of therapy. Despite rapid relief of symptoms in patients with acute decompensated heart failure, after intravenous use of loop diuretics, the use of these agents has been consistently associated with adverse events, including hypokalemia, azotemia, hypotension, and increased mortality. Two recent randomized trials have shown that continuous infusions of loop diuretics did not offer benefit but were associated with adverse events, including hyponatremia, prolonged hospital stay, and increased rate of readmissions. This is probably due to the limitations of congestion evaluation as well as to the deleterious effects linked to drug administration, particularly at higher dosage. The impaired renal function often associated with this treatment is not extensively explored and could deserve more specific studies. Several questions remain to be answered about the best diuretic modality administration, global clinical impact during acute and post-discharge period, and the role of renal function deterioration during treatment. Thus, if loop diuretics are a necessary part of the treatment for acute heart failure, then there must be an approach that allows personalization of therapy for optimal benefit and avoidance of adverse events.

Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial.

INTRODUCTION: Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics. METHODS: Subjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge. RESULTS: A total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m(2) P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04). CONCLUSIONS: In the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months. TRIAL REGISTRATION: ClinicalTrials.gov NCT01441245. Registered 23 September 2011.

Poor in-hospital congestion improvement in acute heart failure patients classified according to left ventricular ejection fraction: prognostic implications.

AIMS: Residual congestion in acute heart failure (AHF) is associated with poor prognosis. However, there is a lack of data on the prognostic value of changes in a combined assessment of in-hospital congestion. The present study sought to assess the association between in-hospital congestion changes and subsequent prognosis according to left ventricular ejection fraction (LVEF) classification. METHODS AND RESULTS: Patients (N = 244, 80.3 ± 7.6 years, 50.8% male) admitted for acute HF in two European tertiary care centres underwent clinical assessment (congestion score included dyspnoea at rest, rales, third heart sound, jugular venous distention, peripheral oedema, and hepatomegaly; simplified congestion score included rales and peripheral oedema), echocardiography, lung ultrasound, and natriuretic peptides (NP) measurement at admission and discharge. The primary outcome was a composite of all-cause mortality and/or HF re-hospitalization. In the 244 considered patients (95 HF with reduced EF, 57 HF with mildly reduced EF, and 92 HF with preserved EF), patients with limited improvement in clinical congestion score (hazard ratio 2.33, 95% CI 1.51-3.61, P = 0.0001), NP levels (2.29, 95% CI 1.55-3.38, P < 0.0001), and the number of B-lines (6.44, 95% CI 4.19-9.89, P < 0.001) had a significantly higher risk of outcome compared with patients experiencing more sizeable decongestion. The same pattern of association was observed when adjusting for confounding factors. A limited improvement in clinical congestion score and in the number of B-lines was related to poor prognosis for all LVEF categories. CONCLUSION: In AHF, the degree of congestion reduction assessed over the in-hospital stay period can stratify the subsequent event risk. Limited reduction in both clinical congestion and B-lines number are related to poor prognosis, irrespective of HF subtype.

Usefulness of Combined Ultrasound Assessment of E/e' Ratio, Pulmonary Pressure, and Cava Vein Status in Patients With Acute Heart Failure.

Congestion is poorly investigated by ultrasound scans during acute heart failure (AHF) and systematic studies evaluating ultrasound indexes of cardiac pulmonary and systemic congestion during early hospital admission are lacking. We aimed to investigate the prevalence of ultrasound cardiac pulmonary and systemic congestion in a consecutive cohort of hospitalized patients with AHF, analyzing the relevance of each ultrasound congestion component (cardiac, pulmonary, and systemic) in predicting the risk of death and rehospitalization. This is a prospective research study of a single center that evaluates patients with an AHF diagnosis who are divided according to the left ventricular ejection fraction in patients with heart failure with preserved ejection fraction or reduced ejection fraction. We performed a complete bedside echocardiography and lung ultrasound analyses within the first 24 hours of hospital admission. The ultrasound congestion score was preliminarily established by measuring the following parameters: cardiac congestion, which was defined as the contemporary presence of E/e' >15 and pulmonary systolic pressure >35 mm Hg and the pulmonary congestion, defined as the total B-line number >25 at the lung ultrasound performed in 8 chest sites; moreover, the systemic congestion was defined if the inferior vena cava (IVC) was >21 mm and if it was associated with a reduced inspiratory collapse >50%. We thoroughly assessed 230 patients and evaluated their results. Of these patients, 135 had heart failure with reduced ejection fraction and there were 95 patients with heart failure with preserved ejection fraction; 122 patients experienced adverse events during the 180-day follow-up. The receiver operating characteristic curve analysis showed that the tricuspid annular peak systolic excursion (TAPSE) (area under the curve [AUC] 0.34 [0.26 to 0.41], p <0.001), E/e' (AUC 0.62 [0.54 to 0.69], p = 0.003), and IVC (AUC 0.70 [0.63 to 0.77], p <0.001) were all significantly related to poor prognosis detection. The univariate Cox regression analysis revealed that cardiac congestion in terms of E/e' and pulmonary systolic pressure (hazard ratio [HR] 1.49 [1.02 to 2.17], p = 0.037), TAPSE (HR 0.90 [0.85 to 0.94], p <0.001), and systemic congestion (HR 2.64 [1.53 to 4.56], p <0.001) were all significantly related to the 180-day outcome. After adjustment for potential confounders, only TAPSE (HR 0.92 [0.88 to 0.98], p = 0.005) and IVC (HR 1.92 [1.07 to 3.46], p = 0.029) confirmed their prognostic role. The multivariable analysis of multiple congestion levels in terms of systemic plus cardiac (HR 1.54 [1.05 to 2.25], p = 0.03), systemic plus pulmonary (HR 2.26 [1.47 to 3.47], p <0.001), and all 3 congestion features (HR 1.53 [1.06 to 2.23], p = 0.02) revealed an incremental prognostic role for each additional determinant. In conclusion, among the ultrasound indexes of congestion, IVC and TAPSE are related to adverse prognosis, and the addition of pulmonary and cardiac congestion indexes increases the risk prediction accuracy. Our data confirmed that right ventricular dysfunction and systemic congestion are the most powerful predictive factors in AHF.

Multi-modality assessment of congestion in acute heart failure: Associations with left ventricular ejection fraction and prognosis.

BACKGROUND: Integrating clinical examination with ultrasound measures of congestion could improve risk stratification in patients hospitalized with acute heart failure (AHF). AIM: To investigate the prevalence of clinical, echocardiographic and lung ultrasound (LUS) signs of congestion according to left ventricular ejection fraction (LVEF) and their association with prognosis in patients with AHF. METHODS: We pooled the data of four cohorts of patients (N = 601, 74.9±10.8 years, 59 % men) with AHF and analysed six features of congestion at enrolment: clinical (peripheral oedema and respiratory rales), biochemical (BNP/NT-proBNP≥median), echocardiographic (inferior vena cava (IVC)≥21 mm, pulmonary artery systolic pressure (PASP)≥40 mmHg, E/e'≥15) and B-lines ≥25 (8-zones) in those with reduced (<40 %, HFrEF), mildly reduced (40-49 %, HFmrEF and preserved (≥50 %HFpEF) LVEF. RESULTS: Compared to patients with HFmrEF (n = 110) and HFpEF (n = 201), those with HFrEF (N = 290) had higher natriuretic peptides, but prevalence of clinical (39 %), echocardiographic (IVC≥21 mm: 56 %, E/e'≥15: 57 %, PASP≥40 mmHg: 76 %) and LUS (48 %) signs of congestion was similar. In multivariable analysis, clinical (HR: 3.24(2.15-4.86), p < 0.001), echocardiographic [(IVC≥21 mm (HR:1.91, 1.21-3.03, p=0.006); E/e'≥15 (HR:1.54, 1.04-2.28, p = 0.031)] and LUS (HR:2.08, 1.34-3.24, p = 0.001) signs of congestion were significantly associated with all-cause mortality and/or HF re-hospitalization. Adding echocardiographic and LUS features of congestion to a model than included age, sex, systolic blood pressure, clinical congestion and natriuretic peptides, improved prediction at 90 and 180 days. CONCLUSIONS: Clinical and ultrasound signs of congestion are highly prevalent in patients with AHF, regardless of LVEF and their combined assessment improves risk stratification.

Prognostic implication of lung ultrasound in heart failure: pooled analysis of international cohorts.

BACKGROUND: Lung ultrasound (LUS) is often used to assess congestion in heart failure (HF). In this study, we assessed the prognostic role of LUS in HF patients at admission and hospital discharge, and in an out-patient setting and explored whether clinical factors (age, sex, left ventricular ejection fraction (LVEF) and atrial fibrillation) impact the prognostic value of LUS findings. Further, we assessed the incremental prognostic value of LUS on top of AHEAD and MAGGIC clinical risk scores. METHODS AND RESULTS: We pooled data of patients hospitalized for HF or followed-up in out-patient clinics from international cohorts. We enrolled 1,947 patients, at admission (n=578), discharge (n=389) and in out-patient clinic (n=980). Total LUS B-line count was calculated for the 8-zone scanning protocol. The primary outcome was a composite of re-hospitalization for HF and all-cause death. Compared to those in the lower tertiles of B-lines, patients in the highest tertile were older, more likely to have signs of HF and higher NT-proBNP levels. A higher number of B-lines was associated with increased risk of primary outcome at discharge (Tertile3 vs Tertile1: adjustedHR= 5.74 (3.26- 10.12), p<0.0001) and in out-patients (Tertile3 vs Tertile1: adjustedHR= 2.66 (1.08- 6.54), p=0.033). Age and LVEF did not influence the prognostic capacity of LUS in different clinical settings. Adding B-line count to MAGGIC and AHEAD scores improved net reclassification significantly in all three clinical settings. CONCLUSION: A higher number of B-lines in patients with HF was associated with increased risk of morbidity and mortality, regardless of the clinical setting.

The role of natriuretic peptides for the diagnosis of left ventricular dysfunction.

Natriuretic peptides (NPs) are entered in current guidelines for heart failure (HF) diagnosis and management because of their high specificity and sensibility in screening patients with acute dyspnea. Due to their availability and relatively low cost, they became the first step examinations in HF patients evaluation at hospital admission together with clinical and chest radiography examination. NPs are released following any cardiac haemodynamic stress due to volume or pressure overload and should be considered as a mirror of cardiac condition helping in recognizing patients with poor outcome. Moreover, the exact role of NPs in early HF stages, in isolated diastolic dysfunction, and in general population is questioned. Several promising reports described their potential role; however, the wide cut-off definition, inclusion criteria, and intrinsic measurement biases do not actually consent to their clinical application in these settings. A multimodality strategy including both NPs and imaging studies appears to be the best strategy to define the cardiac dysfunction etiology and its severity as well as to identify patients with higher risk. In this review, we describe the current and potential role of NPs in patients with asymptomatic cardiac insufficiency, evaluating the requirement to obtain a better standardization for imaging as for laboratory criteria.

Pulmonary Artery Systolic Pressure and Cava Vein Status in Acute Heart Failure with Preserved Ejection Fraction: Clinical and Prognostic Implications.

BACKGROUND: Peak tricuspid regurgitation (TR) velocity and inferior cava vein (ICV) distention are two recognized features of increased pulmonary artery pressure (PASP) and right atrial pressure, respectively. Both parameters are related to pulmonary and systemic congestion and adverse outcomes. However, few data exist about the assessment of PASP and ICV in acute patients affected by heart failure with preserved ejection fraction (HFpEF). Thus, we investigated the relationship existing among clinical and echocardiographic features of congestion, and we analyzed the prognostic impact of PASP and ICV in acute HFpEF patients. METHODS AND RESULTS: We analyzed clinical congestion PASP and ICV value in consecutive patients admitted in our ward by echocardiographic examination using peak Doppler velocity tricuspid regurgitation and ICV diameter and collapse for the assessment of PASP and ICV dimension, respectively. A total of 173 HFpEF patients were included in the analysis. The median age was 81 and median left ventricular ejection fraction (LVEF) was 55% [50-57]. Mean values of PASP was 45 mmHg [35-55] and mean ICV was 22 [20-24] mm. Patients with adverse events during follow-up showed significantly higher values of PASP (50 [35-55] vs. 40 [35-48] mmHg, (p = 0.005) and increased values of ICV (24 [22-25] vs. 22 [20-23] mm, p < 0.001). Multivariable analysis showed prognostic power of ICV dilatation (HR 3.22 [1.58-6.55], p = 0.001) and clinical congestion score ≥ 2 (HR 2.35 [1.12-4.93], p = 0.023), but PASP increase did not reach statistical significance (p = 0.874). The combination of PASP > 40 mmHg and ICV > 21 mm was capable of identifying patients with increased events (45% vs. 20%). CONCLUSIONS: ICV dilatation provides additional prognostic information with respect to PASP in patients with acute HFpEF. A combined model adding PASP and ICV assessment to clinical evaluation is a useful tool for predicting HF related events.

[Pacemaker infection in fragile patients]. / Herzschrittmacherinfektion bei fragilen Patienten.

Complications associated with cardiac implantable electric devices (CIED) are manifold. They include lead dislocation, twiddler's syndrome, device malfunction, haematoma formation and infection. Infections can be divided into acute, subacute and late infections. Both the time of onset and the route of infection play a crucial role. The consequences of a CIED infection are devastating. The most modern treatment methods include the removal of all implanted implants. If complete removal is not followed in the event of infection, there is a high rate of infection recurrence. Open thoracic surgery to remove infected CIED hardware has been replaced by percutaneous lead extraction procedures. Lead extraction requires specialised equipment and expertise and may not be readily available or feasible for some patients. Each extraction procedure is associated with a small risk of potentially fatal complications (e.g. cardiac avulsion, vascular avulsion, haemothorax and cardiac tamponade). For these reasons, the performance of such procedures should be limited to centres with adequate equipment and experience. Successful salvage of CIED systems with in situ sterilisation of contaminated hardware has been reported. In our case, we report the successful salvage of an exposed generator in a frail patient treated more than 5 years after the last generator replacement.

The Conundrum of HFpEF Definition: Non-Invasive Assessment Uncertainties and Alternative Diagnostic Strategies.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome including several morphological phenotypes and varying pathophysiological mechanisms. The conventional classification of HF based on left ventricular ejection fraction (LVEF) has created an oversimplification in diagnostic criteria. Although LVEF is a standardized parameter easy to calculate and broadly applied in the large clinical trials, but it is erroneously considered an index of left ventricular (LV) systolic function. Indeed, it is affected by preload and afterload and it has limitations related to reproducibility, reduced sensitivity and scarce prognostic values especially when above 50%. Notably, additional diagnostic parameters have been recently proposed in order to improve diagnostic accuracy and to homogenize the different HFpEF populations. Unfortunately, these algorithms comprise sophisticated measurements that are difficult to apply in the daily clinical practice. Additionally, the scarce diffusion of these diagnostic criteria may have led to neutral or negative results in interventional phase 3 trials. We propose changes to the current HFpEF diagnostic approach mainly based on LVEF stratification measurement aiming towards a more inclusive model taking into consideration an integrative approach starting from the main diseases responsible for cardiac dysfunction through to cardiac structural and functional alterations. Accordingly, with recent universal HF definitions, a stepwise model could be helpful in recognizing patients with early vs. overt HFpEF by the appraisal of specific Doppler echocardiographic variables. Thus, we would encourage the application of new criteria in order to better identify the different phenotypes and to move towards more personalized medicine.

Different right ventricular dysfunction and pulmonary coupling in acute heart failure according to the left ventricular ejection fraction.

BACKGROUND: Right ventricular (RV) dysfunction and pulmonary uncoupling are two acknowledged features associated with poor outcome, however few data defined RV adaptation across the different left ventricular ejection fraction (EF) cut-off. Additionally, less data are reported in patients with acute heart failure (AHF). AIMS: The aim of present study was to analyse RV function in AHF patients presenting with either reduced or preserved EF. METHODS: This is a multi-center observational study including 380 patients affected by AHF: 235 had AHF with reduced EF (AHFrEF) and 145 had AHF with preserved EF (AHFpEF). Pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion (TAPSE), S' wave velocity, and the RV end-diastolic diameter (RVEDD) were measured by echocardiography. TAPSE/PASP and S'/PASP ratios were calculated as non-invasive surrogates of RV-pulmonary arterial coupling. RESULTS: Factors associated with poor outcome were higher values of PASP (45 [40-55] mmHg vs 40 [35-46] mmHg; p < 0.001), RVEDD (44 [38-47] mm vs 37 [35-42] mm; p < 0.001), lower TAPSE values (17 [15-20] mm vs 20 [18-22] mm; p < 0.001) and S' wave (10 [8-12] cm/s vs 11 [10-13] cm/s; p < 0.001), reduced TAPSE/PASP (0.37 [0.29-0.47] vs 0.50 [0.40-0.60]; p < 0.001) and S'/PASP ratios (0.22 [0.18-0.28] vs 0.28 [0.22-0.34]; p < 0.001). However, the prognostic parameters differed according to the LVEF value: in AHFpEF S'/PASP between 0.22 and 0.29 and > 0.29 demonstrated a protective prognostic value (Respectively HR 0.29 (0.16-0.53), p < 0.001 and HR 0.22 [0.12-0.42], p < 0.001). Conversely, in AHFrEF, TAPSE <16 mm (HR 2.59 [1.67-4.03], p < 0.001), ICV > 21 mm (HR 1.17 [1.17-1.28], p = 0.001) and TAPSE/PASP <0.49 HR 1.92 [1.10-3.37], p = 0.023) were related to adverse outcome. CONCLUSIONS: RV adaptation and RV pulmonary coupling differ in AHF according to the level of LVEF. S' wave, and S'/PASP are associated with adverse outcome in patients with preserved EF; reduced TAPSE and TAPSE/PASP are better prognostic predictors in patients with reduced EF.